Project Summary/Abstract: Core C 20 of the 44 laboratories within the proposed UCSF-NORC employ some aspect of genetics, or genetic manipulation in their research. Some conduct studies to uncover genetic pathways directly associated with alterations in feeding behavior, metabolism or nutritional homeostasis associated with obesity and its health complications in humans. Others use well-defined animal models to study the mechanisms underlying those processes. The targeted alteration of genes within those model organisms is a common method to test molecular hypotheses in those pathways. Still others use expression profiling of samples from humans, model organisms or cell lines to establish candidate pathways involved in energy balance. The UCSF-NORC Genetics and Genomics Core aims to provide access to, assistance with, and training in the use of an array of sophisticated methods and instruments for the genetics and genomics aspects of these studies. Those facilities are distributed amongst five administrative units at UCSF. The proposed NORC Genetics and Genomics Core will create a common infrastructure from which those facilities are coordinated towards NORC research needs. The mechanisms for doing so include processes that facilitate the entry into Genetics and Genomics research by the NORC user base. The putative NORC also is designed to encourage the facilities to develop genetics and genomics technologies that a well-defined process determines to be of emerging need to the UCSF-NORC research base. The NORC Genetics and Genomics Core will provide tools and facilities for: 1. Genome-wide analysis of DNA, RNA or other genomic marks in relationship to genetic kindreds or associations the phenotypic traits in humans (Core A) and model organisms (Core B). 2. Global expression analyses to uncover relevant pathways in laboratory interventional studies. 3. Enabling functional studies that involve genetic interventions in model organisms and cell lines including targeted knock-outs/ins, transgenics, or the viral delivery of genes or shRNAs that target their RNA. 4. Maintaining and introducing animal models of need to NORC research. Overall, this Core will lower methodological barriers to help NORC researchers achieve the efficient and proper application of genetics and genomics tools. These capabilities will accelerate a variety of diverse and interrelated studies in of obesity, nutrition, food intake and metabolism.